A high proportion of patients suffering from an acute stress, e.g. a stroke or a myocardial infarction, develops hyperglycemia, even if these patients have not earlier been diagnosed for diabetes. Such stress-induced hyperglycemia is associated with a high risk of mortality after both stroke and myocardial infarction. Moreover, stress-induced hyperglycemia may be a risk factor for brain damage (cf. Sarah E. Capes et al., Stroke 2001, 32, page 2426).
Additionally, hyperglycemia and insulin resistance are common in critically ill patients in general, even when glucose homeostasis has previously been normal (cf. US 2005/171503, incorporated by reference).
G. Van den Berghe et al. (N. Engl. J. Med. 2001, 345, 1359-1367) found that even moderate hyperglycemia in diabetic as well as in non-diabetic critically ill patients is directly or indirectly harmful to vital organs and systems. Intensive insulin therapy reduced overall ICU (Intensive Care Unit) mortality from 8% to 4.6%, and from 20.2% to 10.6% among patients requiring more than five days intensive care. The intensive insulin therapy also significantly reduced blood stream infections, prolonged inflammation, acute renal failure, critical illness polyneuropathy and transfusion requirements. Hence, strict maintenance of normoglycemia with intensive insulin therapy reduces intensive care and hospital mortality and morbidity of critically ill adult patients in an ICU.
However, intensive insulin therapy requires knowledge of patient blood sugar levels which involves frequently obtaining (capillary) blood samples. This necessitates considerable nurse or technician time and many patients, especially non-diabetics, find repeated blood sampling objectionable. Furthermore, intermittent blood samples may not be done often enough to give an accurate picture of blood sugar levels. Other disadvantages of intensive insulin therapy include: an increase in hypoglycaemia risk (it is known in the art that hypoglycaemia increases the risk of myocardial infarction and ventricular arrhythmia; cf. US 2005/171503, incorporated by reference), sedation can mask hypoglycaemia and differences in opinions of when to introduce insulin and in which patients to apply the protocol.
Hence, although insulin therapy has certainly advantages for critically ill patients as is discussed above, there is still a need in the art to provide a method for controlling insulin administration to critically ill patients, in particular critically ill patients suffering from acute stress.
Acute renal failure (ARF) is a clinical syndrome characterized by rapid deterioration of renal function that occurs within days. ARF is frequently caused by acute tubular necrosis (ATN), which results from ischemic and/or nephrotoxic insults. In the general world population, about 200 cases of severe ARF per million population occur annually. Several drugs, e.g. anti-oxidants, calcium channel blockers, diuretics, vasoactive substances, growth factors, and anti-inflammatory agents, have been investigated on their efficacy in clinical trials but have been found of little or no clinical use.
U.S. Pat. Nos. 5,300,496, 5,527,790, 5,620,967, 5,866,563 and 5,888,993, all incorporated by reference, disclose the use of vanadium compounds in the treatment of diabetes mellitus, hypertension, obesity and similar conditions related to chronically enhanced blood sugar levels.
U.S. Pat. No. 5,885,980, incorporated by reference, discloses a pharmaceutical composition for the treatment of diabetes, said pharmaceutical composition comprising a VO2+ generating compound and micronized glyburide. Example 5 of U.S. Pat. No. 5,885,980 discloses the treatment of a type I diabetic female patient who was hospitalized in an ICU for chronic hyperglycemia with a combination of insulin, vanadyl sulfate and glynase, an anti-diabetic drug of the sulfonylureum type which is more commonly used for the treatment of type II diabetes. However, glynase may cause hypoglycemia and a hypoglycaemia defined as blood glucose below 0.3 mM/l is to increases the risk of myocardial infarction and ventricular arrhythmia (cf. US 2005/171503).
U.S. Pat. No. 6,287,586, incorporated by reference, discloses a pharmaceutical composition of particular vanadium biguanide complexes for the treatment of hyperglycemia and related disorders.
U.S. Pat. No. 6,579,540, incorporated by reference, discloses the use of physiologically acceptable vanadium compounds for the prophylactic treatment of secondary injury of tissue, wherein said secondary injury is the result of a primary injury and wherein the primary injury is caused by a trauma, e.g. reperfusion after ischemia (infarction). U.S. Pat. No. 6,579,540 does therefore not disclose the use of the physiologically acceptable vanadium compounds in the treatment of hyperglycemia or renal ischemia-reperfusion in critically ill patients.
U.S. Pat. No. 6,852,760, incorporated by reference, discloses the use of a combination of a sulfonyl ureum compound, a biologically available source of chromium and a biologically available source of vanadium for the treatment of diabetes.
Consequently, the use of vanadium compounds in controlling hyperglycemia in diabetic patients is known in the art. However, diabetes is a chronic disease. Critically ill patients are, however, hospitalized for a relatively short period of time, in particular one to several days, and in particular in an intensive care unit (ICU). Hence, diabetic patients are a different class of patients than critically ill patients.
P. A. McCullough, Int. J. Nephrol., Volume 2011, Article ID 762590 (doi: 10.4061/2011/762590) suggest that there is an interrelationship between cardiovascular disorders and renal disorders. This relationship is referred to as “cardio-renal”-disorders.
Currently, contrast-induced, preferably radio-contrast-induced nephropathy is treated with N-acetylcysteine.